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11. 发明申请

WO1998024438A1 USE OF NK-1 RECEPTOR ANTAGONISTS FOR TREATING MAJOR DEPRESSIVE DISORDERS 审中-公开
标题翻译：使用NK-1受体拮抗剂治疗主要的恶性疾病
公开(公告)号：WO1998024438A1
公开(公告)日：1998-06-11
申请号：PCT/EP1997006682
申请日：1997-11-25
申请人： MERCK SHARP & DOHME LIMITED , BAKER, Raymond , CURTIS, Neil, Roy , ELLIOTT, Jason, Matthew , HARRISON, Timothy , HOLLINGWORTH, Gregory, John , JACKSON, Philip, Stephen , KULAGOWSKI, Janusz, Jozef , RUPNIAK, Nadia, Melanie , SEWARD, Eileen, Mary , SWAIN, Christopher, John , WILLIAMS, Brian, John
发明人： MERCK SHARP & DOHME LIMITED
IPC分类号： A61K31/535
CPC分类号： A61K31/661 , A61K31/00 , A61K31/395 , A61K31/438 , A61K31/445 , A61K31/451 , A61K31/5375 , A61K31/5377 , A61K31/675 , C07D211/56 , C07D491/10
摘要： The present invention provides the use of a CNS-penetrant NK-1 receptor antagonist in an oral, once-a-day medicament for the treatment of major depressive disorder, methods of treatment using such a NK-1 receptor antagonist and pharmaceutical compositions comprising it.
摘要翻译：本发明提供了CNS渗透性NK-1受体拮抗剂在口服，一日一次的药物中用于治疗重度抑郁障碍的用途，使用这种NK-1受体拮抗剂的治疗方法和包含它的药物组合物。

12. 发明申请

WO1998013369A1 SPIRO-AZACYCLIC DERIVATIVES, THEIR PREPARATION AND THEIR USE AS TACHYKININ ANTAGONISTS 审中-公开
标题翻译：丝裂霉素衍生物，其制备方法及其作为TACHYKININ ANTAGONISTS的用途
公开(公告)号：WO1998013369A1
公开(公告)日：1998-04-02
申请号：PCT/GB1997002532
申请日：1997-09-18
申请人： MERCK SHARP & DOHME LIMITED , HAWORTH, Karen, Elizabeth , SEWARD, Eileen, Mary , SWAIN, Christopher, John
发明人： MERCK SHARP & DOHME LIMITED
IPC分类号： C07D491/107
CPC分类号： C07D491/10
摘要： Substituted spiro-azacyclic derivatives of structural formula (I), wherein R represents hydrogen, hydroxy, C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl optionally substituted alkyl, optionally substituted alkoxy, C2-6alkenyloxy, C3-7cycloalkoxy, phenoxy, benzyloxy, cyano, halogen, NR COR , NR R , SR , SOR , SO2R or OSO2R ; R represents hydrogen, halogen, C1-6alkyl or C1-6alkoxy; or when R is adjacent to R , they may be joined together such that there is formed a 5- or 6-membered saturated or unsaturated ring containing one or two oxygen atoms; R represents an optionally substituted 5- or 6-membered aromatic heterocyclic group containing 1, 2, 3 or 4 heteroatoms, selected from nitrogen, oxygen and sulphur; R represents hydrogen, halogen, C1-6alkyl, C1-6alkoxy, trifluoromethyl, trifluoromethoxy, nitro, cyano, SR , SOR , SO2R , CO2R , CONR R , C2-6alkenyl, C2-6alkynyl or C1-4alkyl substituted by C1-4alkoxy; R represents hydrogen, halogen, C1-6alkyl, trifluoromethyl or C1-6alkoxy substituted by C1-4alkoxy; R represents hydrogen, COR , CO2R , COCONR R , COCO2R , optionally substituted C1-6alkyl; or R represents a group of the formula -CH2CCCH2NR R ; or R represents C1-6alkyl, optionally substituted by oxo, substituted by a 5-membered or 6-membered heterocyclic ring containing 1, 2 or 3 nitrogen atoms optionally substituted by =O or =S and optionally substituted by a group of the formula ZNR R ; R and R each independently represents hydrogen, halogen, C1-6alkyl, CH2OR , oxo, CO2R or CONR R ; p is zero or 1; q is 1 or 2; and X represents -CH2- or -CH2CH2-; Y represents -CH=, -CH2-, -CH2CH= or -CH2CH2-, with the proviso that the sum total of carbon atoms in X+Y is 2 or 3; and when X is -CH2- and Y is -CH= or -CH2CH=, the broken line represents a double bond; or a pharmaceutically acceptable salt thereof, are tachykinin receptor antagonists of use, for example, in the treatment or prevention of pain, inflammation, migraine, emesis and postherpetic neuralgia.
摘要翻译：取代的结构式（I）的螺 - 氮杂环衍生物，其中R 1表示氢，羟基，C 1-6烷基，C 2-6烯基，C 3-7环烷基任选取代的烷基，任选取代的烷氧基，C 2-6烯氧基，C 3-7环烷氧基，苯氧基，苄氧基，氰基，卤素，NR 11 COR 14，NR a R b，SR a，SOR a，SO 2 R a或OSO 2 R a; R 2表示氢，卤素，C 1-6烷基或C 1-6烷氧基; 或当R 2与R 1相邻时，它们可以连接在一起，使得形成含有一个或两个氧原子的5-或6-元饱和或不饱和环; R 3表示含有1,2,3或4个选自氮，氧和硫的杂原子的任选取代的5元或6元芳族杂环基; R 4表示氢，卤素，C 1-6烷基，C 1-6烷氧基，三氟甲基，三氟甲氧基，硝基，氰基，SR a，SOR a，SO 2 R a，CO 2 R a，CONR C 2-6烯基，C 2-6炔基或被C 1-4烷氧基取代的C 1-4烷基; R 5表示氢，卤素，C 1-6烷基，三氟甲基或被C 1-4烷氧基取代的C 1-6烷氧基; R 6表示氢，COR a，CO 2 R a，COCONR a R b，COCO 2 R a，任选取代的C 1-6烷基; 或R 6表示式-CH 2 CCl 2 NR 7 R 8的基团; 或R 6表示任选被氧代取代的C 1-6烷基，被含有1,2或3个氮原子的5元或6元杂环取代，任选被= O或= S取代，并且任选地被一组式ZNR 7 R 8; R 9和R 10各自独立地表示氢，卤素，C 1-6烷基，CH 2 OH，氧代，CO 2 R a或CONR a R b; p为零或1; q为1或2; 并且X表示-CH 2 - 或-CH 2 CH 2 - ; Y表示-CH =，-CH 2 - ， - CH 2 CH =或-CH 2 CH 2 - ，条件是X + Y中的碳原子总和为2或3; 当X为-CH 2 - 且Y为-CH =或-CH 2 CH =时，虚线为双键; 或其药学上可接受的盐是速激肽受体拮抗剂，例如用于治疗或预防疼痛，炎症，偏头痛，呕吐和带状疱疹后神经痛。

13. 发明申请

WO1997049710A1 SPIRO-PIPERIDINE DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS 审中-公开
标题翻译：螺旋哌啶衍生物及其作为治疗剂的用途
公开(公告)号：WO1997049710A1
公开(公告)日：1997-12-31
申请号：PCT/GB1997001630
申请日：1997-06-17
申请人： MERCK SHARP & DOHME LIMITED , BAKER, Raymond , CURTIS, Neil, Roy , ELLIOTT, Jason, Matthew , HARRISON, Timothy , HOLLINGWORTH, Gregory, John , JACKSON, Philip, Stephen , KULAGOWSKI, Janusz, Jozef , SEWARD, Eileen, Mary , SWAIN, Christopher, John , WILLIAMS, Brian, John
发明人： MERCK SHARP & DOHME LIMITED
IPC分类号： C07D491/10
CPC分类号： A61K31/661 , A61K31/395 , A61K31/438 , A61K31/445 , A61K31/451 , A61K31/5375 , A61K31/5377 , A61K31/675 , C07D211/56 , C07D491/10
摘要： Substituted spiro-piperidine derivatives of structural formula (I) are tachykinin receptor antagonists of use, for example, in the treatment or prevention of pain, inflammation, migraine, emesis and postherpetic neuralgia.
摘要翻译：取代的结构式（I）的螺 - 哌啶衍生物是速激肽受体拮抗剂，例如用于治疗或预防疼痛，炎症，偏头痛，呕吐和带状疱疹后神经痛。

14. 发明申请

WO1995030674A1 MORPHOLINE DERIVATIVES AND THEIR USE AS ANTAGONISTS OF TACHIKININS 审中-公开
标题翻译：吗啉衍生物及其作为TACHIKININS的拮抗剂使用
公开(公告)号：WO1995030674A1
公开(公告)日：1995-11-16
申请号：PCT/GB1995000983
申请日：1995-05-01
申请人： MERCK SHARP & DOHME LIMITED , HAWORTH, Karen, Elizabeth , TEALL, Martin, Richard , SEWARD, Eileen, Mary , SWAIN, Christopher, John
发明人： MERCK SHARP & DOHME LIMITED
IPC分类号： C07D413/06
CPC分类号： C07D413/06
摘要： The present invention relates to compounds of formula (I): wherein X is N or CH; and pharmaceutically acceptable salts and prodrugs thereof. The compounds are of particular use in the treatment of pain, inflammation, migraine and emesis.
摘要翻译：本发明涉及式（I）化合物：其中X是N或CH; 及其药学上可接受的盐和前药。该化合物特别用于治疗疼痛，炎症，偏头痛和呕吐。

15. 发明申请

WO1994002461A1 AZACYCLIC COMPOUNDS 审中-公开
标题翻译： AZACYCLIC化合物
公开(公告)号：WO1994002461A1
公开(公告)日：1994-02-03
申请号：PCT/GB1993001525
申请日：1993-07-20
申请人： MERCK SHARP & DOHME LIMITED , SEWARD, Eileen, Mary , SWAIN, Christopher, John
发明人： MERCK SHARP & DOHME LIMITED
IPC分类号： C07D211/42
CPC分类号： C07D401/12 , C07D207/12 , C07D211/42 , C07D211/54 , C07D405/12
摘要： Compounds of Formula (I), and salts and prodrugs thereof, wherein n is 1, 2 or 3; X represents O or S; R1 is optionally substituted phenyl; R2 is aryl or heteroaryl; R4 and R5 are independently H, halo, C1-6alkyl, oxo, CH2ORa, CO2Ra or CONRaRb; R8 represents C(COORa)2, C(CONRaRb)2 or C1-6alkyl substituted by C(=NRa)NRbNRcCO2Rd, CONHNRaRb, C(S)NRaRb, CONRaC1-6alkylR12, CONR13C2-6alkynyl, CONR13C2-6alkenyl, COCONRaRb, CONRaC(NRb)NRcRd, CONR13SO2Ra, SO2NR13CORa, CONRaheteroaryl or CORq; Ra, Rb, Rc and Rd are each H, C1-6alkyl, phenyl or trifluoromethyl. R12 represents ORa, CONRaRb or heteroaryl; R13 represents H or C1-6alkyl; and Rq represents a group (a) where Q represents the residue of a non-aromatic azacyclic or azabicyclic ring system; are tachykinin antagonists useful in therapy.
摘要翻译：式（I）化合物及其盐和前药，其中n为1,2或3; X表示O或S; R1是任选取代的苯基; R2是芳基或杂芳基; R4和R5独立地是H，卤素，C1-6烷基，氧代，CH2ORa，CO2Ra或CONRaRb; R8代表C（COORa）2，C（CONRaRb）2或C（= NRa）NRbNRcCO2Rd，CONHNRaRb，C（S）NRaRb，CONRaC1-6烷基R12，CONR13C2-6炔基，CONR13C2-6烯基，COCONRaRb，CONRaC NRb）NRcRd，CONR13SO2Ra，SO2NR13CORa，杂芳基或CORq; R a，R b，R c和R d各自为H，C 1-6烷基，苯基或三氟甲基。 R 12表示OR a，CONR a R b或杂芳基; R 13表示H或C 1-6烷基; 并且Rq表示基团（a），其中Q表示非芳族氮杂环或氮杂双环体系的残基; 是用于治疗的速激肽拮抗剂。

16. 发明申请

WO1993021181A1 AZACYCLIC COMPOUNDS 审中-公开
标题翻译： AZACYCLIC化合物
公开(公告)号：WO1993021181A1
公开(公告)日：1993-10-28
申请号：PCT/GB1993000788
申请日：1993-04-14
申请人： MERCK SHARP & DOHME LIMITED , BAKER, Raymond , LADDHWAHETTY, Tamara , SEWARD, Eileen Mary , SWAIN, Christopher, John
发明人： MERCK SHARP & DOHME LIMITED
IPC分类号： C07D413/06
CPC分类号： C07D401/06 , C07D207/12 , C07D211/54 , C07D401/12 , C07D403/06 , C07D405/06 , C07D405/12 , C07D409/06 , C07D413/06 , C07D417/06
摘要： Compounds of formula (I), and salts and prodrugs thereof wherein n is 1, 2 or 3; X represents O or S; Y represents a hydrocarbon chain of 1, 2, 3 or 4 carbon atoms optionally substituted by oxo; R is phenyl optionally substituted by 1, 2 or 3 of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, halo, cyano, nitro, trifluoromethyl, trimethylsilyl, -OR , SR , SOR , SO2R , -NR R , -NR COR , -NR CO2R , -CO2R or -CONR R ; R is phenyl, indazolyl, thienyl, furyl, pyridyl, thiazolyl, tetrazolyl, quinolyl, benzhydryl, or benzyl; R and R each independently represent H, halo, C1-6alkyl, oxo, CH2OR , CO2R or CONR R ; R represents an optionally substituted aromatic heterocycle; and R and R are H, trifluoromethyl, C1-6alkyl or phenyl optionally substituted by C1-6alkyl, halo or trifluoromethyl; are tachykinin antagonists useful in medecine.
摘要翻译：式（I）化合物及其盐和前药其中n为1,2或3; X表示O或S; Y表示任选被氧代取代的1,2,3或4个碳原子的烃链; R 1是任选被1,2或3个C 1-6烷基，C 2-6烯基，C 2-6炔基，卤素，氰基，硝基，三氟甲基，三甲基甲硅烷基，-OR a，SR a， a>，SO 2 R a，-NR a R b，-NR a COR b，-NR a CO 2 R b，-CO 2 R a或-CONR a R ; R 2是苯基，吲唑基，噻吩基，呋喃基，吡啶基，噻唑基，四唑基，喹啉基，二苯甲基或苄基; R 4和R 5各自独立地表示H，卤素，C 1-6烷基，氧代，CH 2 OR a，CO 2 R a或CONR a R b; R 8表示任选取代的芳族杂环; R a和R b是H，三氟甲基，C 1-6烷基或任选被C 1-6烷基，卤素或三氟甲基取代的苯基; 是用于药物的速激肽拮抗剂。

17. 发明申请

WO2010138589A1 BICYCLIC PYRIMIDINE PI3K INHIBITOR COMPOUNDS SELECTIVE FOR P110 DELTA, AND METHODS OF USE 审中-公开
标题翻译： PI10K PI3K抑制剂PI3K抑制剂化合物的选择性及其使用方法
公开(公告)号：WO2010138589A1
公开(公告)日：2010-12-02
申请号：PCT/US2010/036199
申请日：2010-05-26
申请人： GENENTECH, INC. , F. HOFFMANN-LA ROCHE AG , CASTANEDO, Georgette , CHAN, Bryan , GOLDSTEIN, David Michael , KONDRU, Rama K. , LUCAS, Matthew C. , PALMER, Wylie Solang , PRICE, Stephen , SAFINA, Brian , SAVY, Pascal Pierre Alexandre , SEWARD, Eileen Mary , SUTHERLIN, Daniel P. , SWEENEY, Zachary Kevin
发明人： CASTANEDO, Georgette , CHAN, Bryan , GOLDSTEIN, David Michael , KONDRU, Rama K. , LUCAS, Matthew C. , PALMER, Wylie Solang , PRICE, Stephen , SAFINA, Brian , SAVY, Pascal Pierre Alexandre , SEWARD, Eileen Mary , SUTHERLIN, Daniel P. , SWEENEY, Zachary Kevin
IPC分类号： C07D487/04 , C07D491/04 , C07D513/04 , A61K31/519 , A61P35/00 , A61P9/00 , A61P29/00 , A61P25/00
CPC分类号： C07D513/04 , C07D487/04 , C07D491/04 , C07D495/04
摘要： Formula (I) ((Ia) and (Ib)) compounds wherein (i) X 1 is N and X 2 is S, (ii) X 1 is CR 7 and X 2 is S, (iii) X 1 is N and X 2 is NR 2 , or (iv) X 1 is CR 7 and X 2 is O, including stereoisomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological, and cancer. Methods of using compounds of Formula (I) for in vitro, in situ , and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
摘要翻译：式（I）（（Ia）和（Ib））化合物，其中（i）X1是N，X2是S，（ii）X1是CR7，X2是S，（iii）X1是N，X2是NR2，或 iv）X1是CR7，X2是O，包括立体异构体，互变异构体，代谢物和药学上可接受的盐，可用于抑制PI3K的δ同种型，以及用于治疗由脂质激酶如炎症，免疫学和癌症介导的病症。公开了使用式（I）化合物在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。

18. 发明申请

WO1998024445A1 USE OF NK-1 RECEPTOR ANTAGONISTS FOR TREATING SCHIZOPHRENIC DISORDERS 审中-公开
标题翻译：使用NK-1受体拮抗剂治疗嗜酸性粒细胞减少症
公开(公告)号：WO1998024445A1
公开(公告)日：1998-06-11
申请号：PCT/EP1997006691
申请日：1997-11-25
申请人： MERCK SHARP & DOHME LIMITED , BAKER, Raymond , CURTIS, Neil, Roy , ELLIOTT, Jason, Matthew , HARRISON, Timothy , HOLLINGWORTH, Gregory, John , JACKSON, Philip, Stephen , KULAGOWSKI, Janusz, Jozef , RUPNIAK, Nadia, Melanie , SEWARD, Eileen, Mary , SWAIN, Christopher, John , WILLIAMS, Brian, John
发明人： MERCK SHARP & DOHME LIMITED
IPC分类号： A61K31/535
CPC分类号： A61K31/661 , A61K31/395 , A61K31/438 , A61K31/445 , A61K31/451 , A61K31/5375 , A61K31/5377 , A61K31/675 , C07D211/56 , C07D491/10
摘要： The present invention provides the use of an orally active, long acting, CNS-penetrant NK-1 receptor antagonist for the manufacture of a medicament adapted for oral administration for the treatment or prevention of schizophrenic disorders, methods of treatment using such a NK-1 receptor antagonist and pharmaceutical compositions comprising it.
摘要翻译：本发明提供口服活性的长效CNS渗透剂NK-1受体拮抗剂在制备适于口服给药以治疗或预防精神分裂症的药物中的用途，使用这种NK-1 受体拮抗剂和包含它的药物组合物。

19. 发明申请

WO1996020197A1 SPIROKETAL DERIVATIVES, COMPOSITIONS CONTAINING THEM AND THEIR USE AS THERAPEUTIC AGENTS 审中-公开
标题翻译：螺旋衍生物，包含它们的组合物及其作为治疗剂的用途
公开(公告)号：WO1996020197A1
公开(公告)日：1996-07-04
申请号：PCT/GB1995002927
申请日：1995-12-15
申请人： MERCK SHARP & DOHME LIMITED , HARRISON, Timothy , OWEN, Simon, Neil , SEWARD, Eileen, Mary , SWAIN, Christopher, John
发明人： MERCK SHARP & DOHME LIMITED
IPC分类号： C07D498/10
CPC分类号： C07D498/10
摘要： The present invention relates to spiroketal derivatives of formula (I) and pharmaceutically acceptable salts thereof wherein R , R , R , R , R , R , R , R , m and n are as defined in the specification, and to processes for their preparation, to intermediates used in their synthesis, to pharmaceutical compositions containing them, and to their use in therapy. The compounds are of particular use in the treatment or prevention of pain, inflammation, migraine, emesis and postherpetic neuralgia.
摘要翻译：本发明涉及式（I）的螺缩酮衍生物及其药学上可接受的盐，其中R 1，R 2，R 3，R 4，R 5，R 6， 9a，R 9b，m和n如说明书中所定义，并且其制备方法，其合成中使用的中间体，含有它们的药物组合物及其在治疗中的用途。该化合物特别用于治疗或预防疼痛，炎症，偏头痛，呕吐和带状疱疹后神经痛。

20. 发明申请

WO1995021819A1 ARALKOXY AND ARALKYLTHIO SUBSTITUTED AZACYCLIC COMPOUNDS AS TACHYKININ ANTAGONISTS 审中-公开
标题翻译：阿卡洛昔康和阿拉奇菌素替代亚甲基化合物作为TACHYKININ拮抗剂
公开(公告)号：WO1995021819A1
公开(公告)日：1995-08-17
申请号：PCT/GB1995000228
申请日：1995-02-06
申请人： MERCK SHARP & DOHME LIMITED , BAKER, Raymond , MACLEOD, Angus, Murray , SEWARD, Eileen, Mary , SWAIN, Christopher, John
发明人： MERCK SHARP & DOHME LIMITED
IPC分类号： C07D211/42
CPC分类号： C07D401/06 , C07D211/42 , C07D211/54
摘要： The present invention relates to compounds of formula (I) wherein n is 1, 2 or 3 and where any carbon atom of (CH2)n may be substituted by R and/or R ; X represents O or S; R represents (CH2)qphenyl, wherein q is 0, 1, 2 or 3, which may be optionally substituted in the phenyl ring; R represents aryl selected from phenyl and naphthyl; heteroaryl selected from indazolyl, thienyl, furyl, pyridyl, thiazolyl, tetrazolyl and quinolyl; benzhydryl; or benzyl; wherein each aryl or heteroaryl moiety may be substituted; R and R each independently represent H, halo, C1-6alkyl, oxo, CO2R or CONR R ; R represents H or C1-6alkyl; R represents trifluoromethyl, C2-6alkenyl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, (CH2)pNR R , CO2R , CONR R , (CH2)pCO2R , (CH2)pCONR R , (CH2)pNR COR , (CH2)pNHSO2R , (CH2)pOR , (CH2)pOC(O)R or (CH2)pOC1-4alkylCOR or C1-6alkyl substituted by a hydroxy group; R represents H, COR , CO2R , COCONR R , COCO2R , C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, C1-6alkyl optionally substituted by a group selected from (CO2R , CONR R , hydroxy, cyano, COR , NR R , C(NOH)NR R , CONHphenyl(C1-4alkyl), COCO2R , CONHNR R , C(S)NR R , CONR C1-6alkylR , CONR C2-6alkynyl, CONR C2-6alkenyl, COCONR R , CONR C(NR )NR R , CONR heteroaryl, and optionally substituted phenyl or C1-6alkyl, optionally substituted by oxo, substituted by an optionally substituted aromatic heterocycle; R and R each independently represent H, C1-6alkyl, trifluoromethyl or phenyl optionally substituted by C1-6alkyl, halo or trifluoromethyl. The compounds are of particular use in the treatment of pain, inflammation, migraine and emesis.
摘要翻译：本发明涉及其中n为1,2或3并且（CH 2）n的任何碳原子可以被R 4和/或R 5取代的式（I）化合物。 X表示O或S; R 1表示（CH 2）q苯基，其中q是0,1,2或3，其可以在苯环中任选被取代; R 2表示选自苯基和萘基的芳基; 选自吲唑基，噻吩基，呋喃基，吡啶基，噻唑基，四唑基和喹啉基的杂芳基。二苯甲基; 或苄基; 其中每个芳基或杂芳基部分可以被取代; R 4和R 5各自独立地表示H，卤素，C 1-6烷基，氧代，CO 2 R a或CONR a R b; R 6表示H或C 1-6烷基; R 7表示三氟甲基，C 2-6烯基，C 3-7环烷基，C 3-7环烷基C 1-4烷基，（CH 2）p NR R 10，CO 2 R 16，CONR 9 R 10，（CH 2） pCO 2 R 16，（CH 2）p CONR 9 R 10，（CH 2）p NR 9 COR 16，（CH 2）p NHSO 2 R 11，（CH 2）pOR 16，（CH 2）pOC O）R 9或（CH 2）pOC 1-4烷基COR 17或被羟基取代的C 1-6烷基; R 8表示H，COR a，CO 2 R a，COCONR a R b，COCO 2 R a，C 3-7环烷基，C 3-7环烷基C 1-4烷基，任选被选定的基团取代的C 1-6烷基由（CO 2 R a，CONR a R b，羟基，氰基，COR a，NR a R b，C（NOH）NR a R b，CONH苯基（C 1 烷基），COCO 2 R a，CONHNR a R b，C（S）NR a R b，CONR a C 1-6烷基R 12，CONR 13 C 2-6炔基， CONR 13 C 2-6烯基，COCONR a R b，CONR a C（NR b）NR a R b，CONR 1杂芳基和任选取代的苯基或C1- 任选被氧代取代的被任选取代的芳族杂环取代的C 1-6烷基; R a和R b各自独立地代表H，C 1-6烷基，三氟甲基或任选被C 1-6烷基，卤素或三氟甲基取代的苯基，化合物是特别用于治疗疼痛，炎症，偏头痛和呕吐。

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